Involvement of programmed necrosis in age-related macular degeneration

• Project/Area Number: 25861637
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Kyushu University
• Principal Investigator: Murakami Yusuke 九州大学, 大学病院, 助教 (50634995)
• Research Collaborator: VAVVAS Demetrios
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 加齢黄斑変性 / 能動的ネクローシス / RIPキナーゼ / RIP kinase / 網膜変性 / ネクローシス / DAMPs

Outline of Final Research Achievements

Double strand RNA (dsRNA) accumulates in the drusen of AMD patient eyes, and has been shown to be implicated in the development of the disease. Here we investigated the mechanisms by which dsRNA causes retinal degeneration in mice. Subretinal injection of dsRNA caused both apoptotic and necrotic photoreceptor cell death, while it mediated necrosis of the retinal pigment epithelium (RPE). These necrotic changes were substantially suppressed by RIP kinase inhibition. Thus, RIP kinase-mediated necrosis is crucial in dsRNA-induced retinal degeneration, and RIP kinase may be a novel therapeutic target for retinal degenerative diseases such as AMD.

Research Products

• [Int'l Joint Research] ハーバード大眼科(米国)
• [Journal Article] Necrotic enlargement of cone photoreceptor cells and the release of high-mobility group box-1 in retinitis pigmentosa (2015)
  • Author(s): Murakami Y, Ikeda Y, Nakatake S, Tachibana T, Fujiwara K, Yoshida N, Notomi S, Nakao S, Hisatomi T, Miller JW, Vavvas DG, Sonoda KH, Ishibashi T
  • Journal Title: Cell Death and Discovery Volume: 1 Issue: 1 Pages: 15058-15058
  • DOI: 10.1038/cddiscovery.2015.58
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Necrotic cone photoreceptor cell death in retinitis pigmetosa (2015)
  • Author(s): Murakami Y, Ikeda Y, Nakatake S, Miller JW, Vavvas DG, Sonoda KH, Ishibashi T.
  • Journal Title: Cell Death and Disease Volume: 31 Issue: 12 Pages: e2038-e2038
  • DOI: 10.1038/cddis.2015.385
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Programmed necrosis, not apoptosis, is a key mediator of cell loss and DAMP-mediated inflammation in dsRNA-induced retinal degeneration (2014)
  • Author(s): Yusuke Murakami, Hidetaka Matsumoto, Miin Roh, Andrea Giani, Keiko Kataoka, Yuki Morizane, Maki Kayama, Aristomenis Thanos, Shunji Nakatake, Shoji Notomi, Toshio Hisatomi, Yasuhiro Ikeda, Tatsuro Ishibashi, Kip Connor, Joan Miller, Demetrios Vavvas
  • Journal Title: Cell death and differentiation Volume: 21(2) Issue: 2 Pages: 270-7
  • DOI: 10.1038/cdd.2013.109
  • Peer Reviewed
• [Presentation] AO-SLOによる網膜色素変性患者の錐体細胞径の解析 (2015)
  • Author(s): 村上祐介、池田康博、中武俊二、立花崇、藤原康太、吉田倫子、中尾新太郎、久冨智朗、石橋達朗
  • Organizer: 日本網膜硝子体学会
  • Place of Presentation: 東京
  • Year and Date: 2015-12-04
• [Presentation] Receptor interacting protein kinase promotes necrosis and enhances inflammation in dsRNA-induced retinal degeneration (2014)
  • Author(s): Yusuke Murakami, Tatsuro Ishibashi, Joan Miller, Demetrios Vavvas
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo
  • Year and Date: 2014-04-03 – 2014-04-06
• [Presentation] Receptor interacting protein kinase promotes necrosis and enhances inflammation in dsRNA-induced retinal degeneration (2014)
  • Author(s): Yusuke Murakami, Tatsuro Ishibashi, Joan Miller, Demetrios Vavvas
  • Organizer: World Ophthalmology Congress
  • Place of Presentation: Tokyo